We have previously demonstrated that intra-blastocoelic injection of purified DS, but not CS, stimulates posterior development, mesoderm formation and neuronal differentiation in an FGF-dependent manner (Hou et al., 2007). Enzymatic degradation of endogenous DS yielded opposite results, which suggests an important role of this GAG in early Xenopus embryos. To better understand the biosynthesis and function of DS, we focused on DS-epi1 and DS-epi2. Using a BLAST search in Xenbase for each gene, we identified two Xenopus laevis homeologs that differ in the derived amino acid sequences by 6% between DS-epi1.S and DS-epi1.L (Fig. S1), and 4% between DS-epi2.S and DS-epi2.L (Fig. S2), and also have well-conserved orthologs in other vertebrates. DS-epi1 and DS-epi2 share a cleavable signal peptide followed by an epimerase domain with 49% identity and two transmembrane domains (Fig. 1A). At the C-terminus, DS-epi2 contains a conserved sulfotransferase-like domain.
